Frequency of prolonged Activated Partial Thromboplastine Time (APTT) in
Liver cirrhosis.
MUKAMIL SHAH1, ABDUL AHAD2, IMRAN UD DIN KHATTAK1
1.
2.
Department of Pathology , Saidu Medical College, Saidu Sharif, Swat
Medicine Saidu Teaching Hospital, Saidu Sharif, Swat
ABSTRACT
BACKGROUND: Liver cirrhosis is very common disease in medical practice. Chronic Liver
disease is marked by the gradual destruction of liver tissues over time. Severe liver disease falls
under this category including cirrhosis of liver and fibrosis. Chronic damage to the liver slowly
replaces normal functioning liver tissue, progressively diminish blood flow though the liver. As
the normal liver tissue is lost, nutrients, horrmones, drugs and poisons are not processed
effectively by the liver. In addition protein production including coagulation factors and other
substances produced by the liver are inhibited. This study was designed to find the relative
frequency of having prolonged APTT in chronic liver disease.
STUDY DESIGN AND PLACE: This cross-sectional study of chronic liver disease was
conducted in the departments of Medicine and Pathology of Saidu Teaching Hospital / Saidu
Medical College, Swat, Pakistan from Feb 15th 2012 to Dec 15th 2012.
MATERIAL AND METHODS: Seventy eight (78) patients of chronic liver disease (38 Males
& 40 Females) were studied. Those on anticoagulants therapy were excluded from the study.
Ethyelenediamine tetra acetic acid and citrated blood samples were taken for tests to be
performed. Blood counts were performed on coulter counter haematology analyzer. APTT,
Prothrombine time (PT), Bleeding time (BT) and thrombin time (TT) were performed manually.
RESULTS: Out of 78 patients of chronic liver disease, prolonged APTT was found in
64(82.05%) patients (28 males and 36 females). 14(17.95%) patients (10 males and 4 females)
were found to have normal APTT.
CONCLUSION: Prolong APTT is significant finding in cirrhosis liver. It should be included in
the investigations for bleeding tendencies of cirrhotic patients.
KEY WORDS: Activated partial thromboplastin time, chronic liver disease, cirrhosis liver.
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INTRODUCTION
Liver cirrhosis is diffuse process in which the normal architecture of liver is converted into
structurally abnormal nodules. In other words, it is the necrosis of the liver followed by fibrosis
and regeneration. Its clinical features are produced by hepatocellular destruction, portal
hypertension and Porto systemic shunting.1 Liver cirrhosis leaves significant morbidity and
mortality in our country, however early diagnosis prevents complications and carries good
prognosis.2
Coagulation disorder in patients with liver disease results from impairment in the clotting and
fibrinolytic system, and reduced number of platelets.3As liver parenchymal cells synthesizes
most of the clotting factors, levels of these procoagulants and anticoagulants as well as
fibrinolytic and antifibrinolytic factors will decrease in plasma. These changes may be reflected
in a minor way in patients with mild chronic liver disease. Thrombocytopenia usually complicate
the clinically picture4. Chronic liver disease especially cirrhosis liver is a major health problem
in tropical countries like Pakistan.
This study was conducted to find the relative frequency of prolonged APTT in patients with this
disease. It will help the hematologist in better understanding the severity of coagulation defects
and their relative complications e.g. bleeding/thrombosis which will lead to better management
of such patients 5, 6.
SUBJECT AND METHODS
A total of 78 patients (38 males and 40 females) were included in this study. These patients were
taken from Medical unit of Saidu Teaching Hospital/Saidu Medical College, Saidu Sharif, Swat,
from Feb 15th, 2011 to Dec 15th, 2011. In each case a detailed history were taken. Thorough
physical & clinical examination was performed.
A primary criterion of inclusion was the presence of cirrhosis liver, irrespective of etiology.
Diagnosis of cirrhosis liver is based on a combination of
a. Clinical features.
b. Biochemical investigation.
c. Abdominal ultrasound.
Cirrhotic patients with previous history of coagulation disorders and the drugs that causes
changes in the coagulation parameters i.e. oral contraceptives, aspirin, heparin, warfarin were
excluded.
All the investigations were performed at Saidu Medical College, Saidu Sharif, Swat Pakistan.
EDTA and citrated blood samples were taken for tests to be performed. Blood counts performed
on coulter counter haematology analyzer. BT, PT, APTT, TT were performed manually.
The statistical software SPSS version 15.0 was used for the analysis of data.
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RESULTS
In this study 78 patients with liver cirrhosis were included. The patients were taken from Medical
ward of Saidu Teaching Hospital Swat. Twenty two normal individuals were included as control.
APTT considered to be prolonged when the patient value was >10 seconds of control. The mean
age of patients with cirrhosis was 57 years. The result of patients and controls are shown, in
Tables: I, II & III.
Table-I shows clinical features such as pallor in 70 (89.74%), ascites in 54(60.23%), edema in
50(64.10%), splenomegaly in 48(61.54%), jaundice in 39 (50.00%) and bleeding in 20(25.64%)
patients.
Table-II shows biochemical investigations. PT was 26.84+1.62 in 38 male patients and it was
13.10 + 0.12 in 14 male controls with P value of < 0.01. PT was 24.85+ 2.37 in 40 female
patients and it was 13.05 + 0.15 in 8 female controls with p value of < 0.01. APTT was 79.30 +
4.20 in 38 male patients and it was 35.00 + 0.23 in 14 male controls with p value of <0.01. APTT
was 79.60 + 13.60 in 14 female patients and it was 35.30 + 0.30 in 8 female controls with P
value of <0.01.
Thrombin Time (TT) was 12.47 + 0.62 in 38 male patients and it was 10.0 + 0.20 in 14 male
controls with p value of <0.05.
Thrombin Time (TT) was 12.70 + 0.98 in 40 female patients and it was 10.5 + 0.23 in 8 female
Controls with p value of <0.05.
Bleeding Time (BT) was 5.00 + 1.20 in 38 male patients and it was 6.30 + 0.40 in 14 male
controls.
Bleeding Time (BT) was 5.20 + 0.73 in 40 female patients and it was 4.00 + 0.45 in 8 female
controls.
Table-III shows that Hb was 10.69 + 0.40 in38 male patients and it was 13.00 + 0.20 in 40 male
Controls with p value of <0.001.
Hb was 9.93 + 0.82 in 40 female patients and it was 12.20 in female controls with P value of <
0.001.
TLC X 106 was 7.10 + 0.95 in 38 male patients and it was 7.00 + 0.40 in 14 male controls.
TLC x 106 was 7.8 + 0.95 in 40 female patients and it was 6.40 + 0.35 in 8 female controls.
Platelet count X 106 was 121 + 8.07 in 38 male patients and it was 289 + 10.0 in 14 male
Controls with p value of <0.001.
Platelet count X 106 was 93.35 + 12.0 in 40 female patients and it was 225 + 13.0 in 8 female
Controls with p value of <0.001.
MCV was 87.71 + 3.28 in 38 male patients and it was 88.5 + 4.0 in 14 male controls with P
value<0.05.
MCV was 93.21 + 2.70 in 40 female patients and it was 79.0 + 6.0 in 8 female controls with P
value < 0.05.
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Table-I : Clinical Findings in Cirrhotic patients .
Pallor
Ascites
Edema
Splenomagly
Jaundice
Bleeding
70(89.74%)
54(69.23%)
50(64.10%)
48(61.54%)
39(50%)
20(25.64%)
Table-II: Prothrombin time, Activated Partial thromboplastin time, Thrombin time and
Bleeding time of controls and patients.
Parameters
Gender
Controls
Patients
P Value
Prothrombine Time (PT)
Sec
Male
(14) 13.10 + 0.12
(38) 26.84 + 1.62
p<0.01
Female
Male
(08) 13.05 + 0.15
(14) 35.00 + 0.23
(40) 24.85 + 2.37
(38) 79.30 + 4.20
p<0.01
p<0.001
Female
(08) 35.30 + 0.30
(40) 79.60 + 13.60
p<0.01
Male
Female
Male
Female
(14) 10.0 + 0.20
(08) 10.5 + 0.23
(14) 6.30 + 0.40
(08) 4.00 + 0.45
(38) 12.47 + 0.62
(40) 12.70 + 0.98
(38) 5.00 + 1.20
(40) 5.20 + 0.73
p<0.05
p<0.05
---
Activated Partial
Thromboplastin Time
(APPT) Sec
Thrombin Time
(TT) Sec
Bleeding Time
(BT) minutes
Table-III: Haemoglobin, Total Leucocytes Count (TLC), Platelets count and Mean
corpuscular
Volume (MCV) in control and patients
Parameters
Gender
Control
Patients
P Value
Male
(14) 13.00 + 0.20
(38) 10.69 + 0.40
p<0.001
Female
(08) 12.20 + 0.24
(40) 9.93 + 0.82
p<0.001
Male
(14) 7.00 + 0.40
(38) 7.10 + 0.95
--
Female
(08) 6.40 + 0.35
(40) 7.8 + 0.95
--
Male
(14) 280 + 10.0
(38) 121 + 8.07
p<0.001
Female
(08) 225 + 13.0
(40) 93.35 + 12.0
p<0.001
Male
(14) 88.5 + 4.0
(38) 87.71 + 3.28
p<0.05
Female
(08) 79.0 + 6.0
(40) 93.21 + 2.70
p<0.05
Hb, (gm/dl)
TLC x 106
Platelets Count X 106
MCV (fl)
Activated partial thombopastin time was prolonged in 64 patients out of 78 (28 males & 36
females). 14 patients were found to have normal APTT.
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Comparison of mean values of activated partial thrombopastin time for patients and controls are
shown in table II. The difference of patients and control values in both patients and controls are
statistically highly significant (P value < 0.001).
The mean value in patients with cirrhosis was 121,000 ± 8.07 platelets/ cmm, which are
significantly lower then the normal range of 150,000 – 450,000/ cmm.
The mean value in patients with cirrhosis was 10.00 ± 0.60 gm/dl which is significantly lower
than the normal range of Hb 12 . 6 gm/dl.
DISCUSSION
Homeostasis is intimately related to liver functions, because most of coagulation factors are
synthesized in liver parenchymal cells and the liver’s reticuloendothelial system caries an
important role in the clearance of activated products. The extent of coagulation abnormalities
depends upon the degree of disturbed liver functions7. Patients with cirrhosis suffer from a
complex haemostatic disturbance, due to abnormalities in clotting and fibrinolytic system called
secondary haemostasis.8
Platelet abnormalities associated with chronic liver disease include thrombocytopenia (decreased
number of platelets) as well as abnormalities in function (thrombosthania) called primary
haemostasis .9
In our study there was significant prolongation of activated partial Thromboplastin time in
patients of liver cirrhosis. This finding is compatible with previous studies10, 11. Prothrombin time
is commonly increased in liver disease because liver is unable to manufacture adequate amount
of clotting factors including those involved in extrinsic pathway.12 Out of factor II, V, VII and X,
factor VII is the rate limiting factor in this pathway and thus has greatest influence on the
Prothrombine time. Fall of factor VII which has shortest half life (6 hours) has bad prognosis. As
liver function worsens, the APTT prolongs, the reason being that factor IX, XI, XII and fibrin
stabilizing factors are also produced by the liver.13 Prolongation of both PT and APTT may be
noted while other biochemical tests of liver function in liver disease are still normal.
Occasionally APTT may be abnormal when the PT is with in normal range. 14
In the present study platelets count was significantly decreased in the patients with hepatic
cirrhosis. These findings are the same as reported in previous studies. 15-16 Thrombocytopenia is
common finding in patients with diagnosed liver disease.17 Severe thrombocytopenia < 30000
associated with spontaneous bleeding is usually not seen in uncomplicated cirrhosis. The
common reason cited for Thrombocytopenia in patients with cirrhosis is spleenomegaly and
portal hypertension.18 Under normal conditions approximately 1/3rd of the circulating platelets
are within the spleen. Spleenomagly and hypersplenism results in thrombocytopenia, although
the total platelets mass may not be reduced. 19, 20
CONCLUSION
It is concluded that significant prolongation of APTT highlights its importance as a reliable
marker of coagulopathies in cirrhotic patients. It should be included in the investigation for
bleeding tendencies of cirrhotic patients.
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Correspondence Address
Dr. Mukamil Shah
Assistant Professor Pathology
Saidu Medical College Saidu Sharif Swat
Cell no. 03439816530.
Email: drmukamilshah@yahoo.com
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